Neisseria meningitidis is a leading cause of meningococcal disease, including meningitis and bacterial septicemia induced shock that affect children and young adults. Vaccines for protecting against meningococcal disease have been described; these include polysaccharide based vaccines, protein vaccines, and meningococcal outer membrane vesicle (OMV) vaccines. Protection against meningococcal disease is measured by the ability of antibody (Ab) in serum to mediate complement-dependent killing of the bacteria. A serum bactericidal titer of 1:4 or greater using human complement is considered protective against invasive disease (Goldschneider et al. (1969) J. Exp. Med. 129:1307-26). However, there is wide variation among individuals within a population in their ability to kill meningococci in complement-dependent bactericidal assays. In some instances, despite high levels of antibody binding, killing does not occur. Antibody directed against certain bacterial targets may not activate complement, and in some instances, may even block killing by otherwise bactericidal Ab.
Moreover, while capsular polysaccharide based vaccines have been successful in immunization against serogroups A, C, W and Y, currently there are no effective licensed vaccines available in the U.S. against serogroup B Neisseria meningitidis. Serogroup B capsular polysaccharide mimics a host molecule (neural-cell adhesion molecule, or N-CAM) (Finne et al., 1983. Lancet 2:355-357) and therefore is not immunogenic. Furthermore, there is concern that Abs elicited against serogroup B capsule may result in autoimmune damage to host neurons.
Efforts to combat epidemics caused by serogroup B meningococci have resulted in development of outer membrane vesicle vaccines. Once such epidemic occurred in Norway. The use of an outer membrane vesicle vaccine to counter this epidemic resulted in ˜57% protection; this was not deemed sufficient to justify a public vaccination campaign (Bjune et al. 1991. Lancet 338:1093-1096). More recently, an outbreak of serogroup B meningococcal disease in New Zealand prompted the manufacture and use of outer membrane vesicle (OMV) vaccines prepared from Neisseria meningitidis, including the MenZB and MenBvac vaccines, that were ‘tailor made’ and used to combat a meningitis epidemic in New Zealand caused by serogroup B Neisseria meningitidis (Wedege E et al. Clin Vaccine Immunol. 2007; 14(7):830-8). However, breakthrough has occurred in cases who have been vaccinated; vaccine efficacy has been reported to be 75% (McNicholas et al., 2008, N Z Med J 121:38-46). Vaccine failures were not attributed to identifiable immunodeficiencies in the host.
Thus, there remains a need for methods for screening individuals at risk for contracting meningococcal disease and/or at risk for failing to elicit a bactericidal response to a vaccine against Neisseria meningitidis, as well as a need for improved immunogenic vaccines against meningococcal disease.